Precursors to social and communication difficulties in infants at-risk for autism: gaze following and attentional engagement

Whilst joint attention (JA) impairments in autism have been widely studied, little is known about the early development of gaze following, a precursor to establishing JA. We employed eye-tracking to record gaze following longitudinally in infants with and without a family history of autism spectrum disorder (ASD) at 7 and 13 months. No group difference was found between at-risk and low-risk infants in gaze following behaviour at either age. However, despite following gaze successfully at 13 months, at-risk infants with later emerging socio-communication difficulties (both those with ASD and atypical development at 36 months of age) allocated less attention to the congruent object compared to typically developing at-risk siblings and low-risk controls. The findings suggest that the subtle emergence of difficulties in JA in infancy may be related to ASD and other atypical outcomes

Arsenic as an Endocrine Disruptor: Arsenic Disrupts Retinoic Acid Receptor–and Thyroid Hormone Receptor–Mediated Gene Regulation and Thyroid Hormone–Mediated Amphibian Tail Metamorphosis

Background: Chronic exposure to excess arsenic in drinking water has been strongly associated with increased risks of multiple cancers, diabetes, heart disease, and reproductive and developmental problems in humans. We previously demonstrated that As, a potent endocrine disruptor at low, environmentally relevant levels, alters steroid signaling at the level of receptor-mediated gene regulation for all five steroid receptors. Objectives: The goal of this study was to determine whether As can also disrupt gene regulation via the retinoic acid (RA) receptor (RAR) and/or the thyroid hormone (TH) receptor (TR) and whether these effects are similar to previously observed effects on steroid regulation. Methods and results: Human embryonic NT2 or rat pituitary GH3 cells were treated with 0.01–5 μM sodium arsenite for 24 hr, with or without RA or TH, respectively, to examine effects of As on receptor-mediated gene transcription. At low, noncytotoxic doses, As significantly altered RAR-dependent gene transcription of a transfected RAR response element–luciferase construct and the native RA-inducible cytochrome P450 CYP26A gene in NT2 cells. Likewise, low-dose As significantly altered expression of a transfected TR response element–luciferase construct and the endogenous TR-regulated type I deiodinase (DIO1) gene in a similar manner in GH3 cells. An amphibian ex vivo tail metamorphosis assay was used to examine whether endocrine disruption by low-dose As could have specific pathophysiologic consequences, because tail metamorphosis is tightly controlled by TH through TR. TH-dependent tail shrinkage was inhibited in a dose-dependent manner by 0.1– 4.0 μM As. Conclusions: As had similar effects on RAR- and TR-mediated gene regulation as those previously observed for the steroid receptors, suggesting a common mechanism or action. Arsenic also profoundly affected a TR-dependent developmental process in a model animal system at very low concentrations. Because RAR and TH are critical for both normal human development and adult function and their dysregulation is associated with many disease processes, disruption of these hormone receptor–dependent processes by As is also potentially relevant to human developmental problems and disease risk

The developmental trajectory of attentional orienting to socio-biological cues.

It has been proposed that the orienting of attention in the same direction as another’s point of gaze relies on innate brain mechanisms which are present from birth, but direct evidence relating to the influence of eye gaze cues on attentional orienting in young children is limited. In two experiments, 137 children aged 3–10 years old performed an adapted pro-saccade task with centrally presented uninformative eye gaze, finger pointing and arrow pre-cues which were either congruent or incongruent with the direction of target presentations. When the central cue overlapped with presentation of the peripheral target (Experiment 1), children up to 5 years old had difficulty disengaging fixation from central fixation in order to saccade to the target. This effect was found to be particularly marked for eye gaze cues. When central cues were extinguished simultaneously with peripheral target onset (Experiment 2), this effect was greatly reduced. In both experiments finger pointing cues (image of pointing index finger presented at fixation) exerted a strong influence on saccade reaction time to the peripheral stimulus for the youngest group of children (<5 years). Overall the results suggest that although young children are strongly engaged by centrally presented eye gaze cues, the directional influence of such cues on overt attentional orienting is only present in older children, meaning that the effect is unlikely to be dependent upon an innate brain module. Instead, the results are consistent with the existence of stimulus–response associations which develop with age and environmental experience

Sex Differences in Social Attention in Infants at Risk for Autism

We studied visual attention to emotional faces in 10-month-old infant siblings of children with ASD (ASD-sibs; N = 70) and a siblings of typically developing children (N = 29) using static stimuli. Contrary to our predictions, we found no evidence for atypical gaze behavior in ASD-sibs when boys and girls were analyzed together. However, a sex difference was found in ASD-sibs' visual attention to the mouth. Male ASD-sibs looked more at the mouth across emotions compared to male controls and female ASD-sibs. In contrast, female ASD-sibs looked less at the mouth compared to female controls. These findings suggest that some aspects of early emerging atypical social attention in ASD-sibs may be sex specific

Cues for Early Social Skills: Direct Gaze Modulates Newborns' Recognition of Talking Faces

Previous studies showed that, from birth, speech and eye gaze are two important cues in guiding early face processing and social cognition. These studies tested the role of each cue independently; however, infants normally perceive speech and eye gaze together. Using a familiarization-test procedure, we first familiarized newborn infants (n = 24) with videos of unfamiliar talking faces with either direct gaze or averted gaze. Newborns were then tested with photographs of the previously seen face and of a new one. The newborns looked longer at the face that previously talked to them, but only in the direct gaze condition. These results highlight the importance of both speech and eye gaze as socio-communicative cues by which infants identify others. They suggest that gaze and infant-directed speech, experienced together, are powerful cues for the development of early social skills